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P E Hughes

Publications and source records attributed to P E Hughes.

At least 19 recordsLinked to original sources
PubMed2005

Increasing the age of gilts at first boar contact improves the timing and synchrony of the pubertal response but does not affect potential litter size.

One hundred and ninety-two Large White/Landrace crossbred gilts were used in this study. The study was conducted in two blocks, with 16 gilts allocated to each of six treatments in each block. The treatments compared the effects on puberty attainment of commencing boar exposure at 161, 182 or 203 days of age, and the effect of first mating gilts at either the pubertal or second oestrus on ovulation rate and early embryo survival. Boar contact took place in a detection-mating area (DMA), and consisted of 20 min/day of full contact with a vasectomized boar greater than ten months of age. Gilts were artificially inseminated at the allocated oestrus, with the reproductive tracts collected at 22.8+/-0.4 days after first mating (mean+/-S.E.M.), and the numbers of corpora lutea and viable embryos recorded. The age at which gilts attained puberty increased with the age at which boar exposure commenced. Mean gilt ages at puberty were 179.5+/-1.6, 191.7+/-1.2 and 210.3+/-0.9 days, respectively, when boar contact commenced at 161, 182 and 203 days of age, P<0.01. Mean days-to-puberty was significantly shorter when boar contact began at 182 and 203 days of age compared to 161 days of age (10.4+/-1.2 and 8.3+/-0.9 days versus 18.9+/-1.5 days, respectively, P<0.01). Similarly, commencing boar exposure at 182 or 203 days of age as opposed to 161 days of age significantly increased the proportion of gilts attaining puberty within 10 days of start of boar exposure (0.67 and 0.70 versus 0.24, P<0.01). Mean days-to-puberty and the synchrony of puberty attainment were similar when boar contact commenced at 182 and 203 days of age. There was no significant effect of mating oestrus or age of gilts at mating on ovulation rate, embryo number or embryo survival. In conclusion, the current data indicate that the timing and synchrony of puberty attainment is significantly improved when first boar exposure of gilts is delayed until 182 days of age. Further, it is evident that within the age range investigated, delaying first mating until the second oestrus does not significantly increase either ovulation rate or embryo number at day 20 post-mating.

Animal Husbandry↗
PubMed2001

Integrin activation controls metastasis in human breast cancer.

Metastasis is the primary cause of death in human breast cancer. Metastasis to bone, lungs, liver, and brain involves dissemination of breast cancer cells via the bloodstream and requires adhesion within the vasculature. Blood cell adhesion within the vasculature depends on integrins, a family of transmembrane adhesion receptors, and is regulated by integrin activation. Here we show that integrin alpha v beta 3 supports breast cancer cell attachment under blood flow conditions in an activation-dependent manner. Integrin alpha v beta 3 was found in two distinct functional states in human breast cancer cells. The activated, but not the nonactivated, state supported tumor cell arrest during blood flow through interaction with platelets. Importantly, activated alpha v beta 3 was expressed by freshly isolated metastatic human breast cancer cells and variants of the MDA-MB 435 human breast cancer cell line, derived from mammary fat pad tumors or distant metastases in severe combined immunodeficient mice. Expression of constitutively activated mutant alpha v beta 3(D723R), but not alpha v beta 3(WT), in MDA-MB 435 cells strongly promoted metastasis in the mouse model. Thus breast cancer cells can exhibit a platelet-interactive and metastatic phenotype that is controlled by the activation of integrin alpha v beta 3. Consequently, alterations within tumors that lead to the aberrant control of integrin activation are expected to adversely affect the course of human breast cancer.

Animals↗
PubMed2000

The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function.

The closely related small GTP-binding proteins H-Ras and R-Ras have opposing effects on the regulation of integrin cell adhesion receptors. To gain insight into the properties of R-Ras with respect to the regulation of integrin function and interactions with downstream effectors we performed an analysis of R-Ras variants containing mutations in the effector binding domain and C-terminal prenylation site. We found that the activation of the downstream effector PI 3-kinase was sensitive to mutations in the effector binding domain, as was the binding to the effectors, Ral-GDS, Raf-1 and the novel effector Nore1. Furthermore, specific mutations in the effector binding loop and C-terminal prenylation motif impaired the ability of R-Ras to regulate integrin function in CHO cells. However, the ability of the R-Ras effector loop mutants to bind, and activate known effectors did not correlate with their ability to regulate integrin function. Thus, the known R-Ras effectors are not critical for regulating integrin activation, at least in CHO cells. Consequently, these studies provide insight into the structural basis of the interactions between R-Ras and its candidate effectors and suggest the existence of novel mechanisms through which this GTPase could regulate cell adhesion.

Amino Acid Sequence↗
PubMed2000

Neuroprotective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases.

There are three main mechanisms of neuronal cell death which may act separately or cooperatively to cause neurodegeneration. This lethal triplet of metabolic compromise, excitotoxicity, and oxidative stress causes neuronal cell death that is both necrotic and apoptotic in nature. Aspects of each of these three mechanisms are believed to play a role in the neurodegeneration that occurs in both Parkinson's and Huntington's diseases. Strategies to rescue or protect injured neurons usually involve promoting neuronal growth and function or interfering with neurotoxic processes. Considerable research has been done on testing a large array of neuroprotective agents using animal models which mimic these disorders. Some of these approaches have progressed to the clinical arena. Here, we review neuroprotective strategies which have been found to successfully ameliorate the neurodegeneration associated with Parkinson's and Huntington's diseases. First, we will give an overview of the mechanisms of cell death and the background of Parkinson's and Huntington's diseases. Then we will elaborate on a range of neuroprotective strategies, including neurotrophic factors, anti-excitotoxins, antioxidants, bioenergetic supplements, anti-apoptotics, immunosuppressants, and cell transplantation techniques. Most of these approaches hold promise as potential therapies in the treatment of these disorders.

Animals↗
PubMed2000

Death effector domain protein PEA-15 potentiates Ras activation of extracellular signal receptor-activated kinase by an adhesion-independent mechanism.

PEA-15 is a small, death effector-domain (DED)-containing protein that was recently demonstrated to inhibit tumor necrosis factor-alpha-induced apoptosis and to reverse the inhibition of integrin activation due to H-Ras. This led us to investigate the involvement of PEA-15 in Ras signaling. Surprisingly, PEA-15 activates the extracellular signal receptor-activated kinase (ERK) mitogen-activated protein kinase pathway in a Ras-dependent manner. PEA-15 expression in Chinese hamster ovary cells resulted in an increased mitogen-activated protein kinase kinase and ERK activity. Furthermore, PEA-15 expression leads to an increase in Ras guanosine 5'-triphosphate loading. PEA-15 bypasses the anchorage dependence of ERK activation. Finally, the effects of PEA-15 on integrin signaling are separate from those on ERK activation. Heretofore, all known DEDs functioned in the regulation of apoptosis. In contrast, the DED of PEA-15 is essential for its capacity to activate ERK. The ability of PEA-15 to simultaneously inhibit apoptosis and potentiate Ras-to-Erk signaling may be of importance for oncogenic processes.

3T3 Cells↗
PubMed1999

A note on the effects of contact frequency and time of day of boar exposure on the efficacy of the boar effect.

Sixty-four Large White/Landrace crossbred gilts were used in this study, 16 gilts being allocated to each of four treatments to compare the effects on puberty attainment of exposure to boar contact either 0, 1 or 2 times daily. The once-daily exposure occurred in either the morning or the afternoon (AM vs. PM). Treatments were of 20-min duration starting at a mean gilt age of 160 days and continuing for 60 days. Boar exposure significantly increased the proportion of gilts attaining puberty within 60 days of the commencement of treatments (P < 0.05) compared with gilts not receiving boar contact. Gilts receiving boar exposure twice daily attained puberty significantly earlier than did gilts in the two treatment groups (AM and PM, respectively) given a single daily boar exposure period (mean gilt ages at puberty 176.4 vs. 192.7 and 189.2 days of age, respectively, P < 0.05). It is concluded that (a) twice-daily boar contact enhances the efficacy of the boar effect in gilts above that seen with a single daily boar exposure period and (b) this enhanced response of the gilt is due to the frequency of boar contact and not to the time of day at which the contact occurs.

Animals↗
PubMed1999

Expression of the activin axis and neuronal rescue effects of recombinant activin A following hypoxic-ischemic brain injury in the infant rat.

Neurotrophic factors are induced in the brain in response to injury and may restrict the extent of neuronal loss and facilitate recovery. We have previously reported a strong neuronal induction of activin betaA subunit mRNA expression after a hypoxic-ischemic (HI) injury in the rat brain. Here, we further extended our studies to examine a role for the activin inhibitory binding protein, follistatin after injury and also to determine the potential of activin as a neuronal rescue agent. Ribonuclease protection assay (RPA) was used to quantify the time course of the mRNA expression of activin betaA subunit and follistatin, following a 60-min HI brain injury. Activin betaA subunit mRNA level increased in the contralateral hemisphere 5 h after injury and returned to normal at 10 h post injury. In contrast, follistatin mRNA levels decreased in the same hemisphere at 5 and 10 h after injury. The effect of intracerebroventrically (i. c.v.) administered recombinant human activin A or its antagonist, inhibin A, on neuronal death after a 15-min HI brain injury was determined for a number of brain regions. One microgram activin A (n=23) reduced the neuronal loss in the hippocampal CA1/2 region, dorsolateral striatum but not in the parietal cortex. In contrast, 1 microg of inhibin A (n=18) did not have a significant effect on the extent of neuronal loss in any of the affected regions. This pattern of neuroprotection was consistent with the distribution of immunoreactivity for the activin receptor type II subunit. These results demonstrate that activin A, but not its functional antagonist inhibin A, can enhance the survival of injured hippocampal and striatal neurons. Since follistatin is thought to exert a neutralising effect on activin A activity, the down-regulation of follistatin expression post injury may be allowing activin A to become more accessible to neurons after injury. Overall, these results suggest a role of the activin axis in modulating the survival of specific populations of injured neurons.

Activins↗
PubMed1999

Genetic and pharmacological analyses of Syk function in alphaIIbbeta3 signaling in platelets.

Agonists induce inside-out alphaIIbbeta3 signaling resulting in fibrinogen binding and platelet aggregation. These in turn trigger outside-in signaling resulting in further platelet stimulation. Because the Syk tyrosine kinase is activated during both phases of integrin signaling, we evaluated its role in alphaIIbbeta3 function in murine platelets rendered null for Syk by gene targeting and in human platelets incubated with piceatannol, a tyrosine kinase inhibitor reportedly selective for Syk. Both Syk null murine platelets and piceatannol-treated human platelets exhibited a partial, but statistically significant defect in activation of alphaIIbbeta3 by adenine diphosphate (ADP) +/- epinephrine as assessed by fibrinogen binding. Syk null platelets adhered normally to immobilized fibrinogen, and mice with these platelets exhibited normal tail bleeding times. In contrast, piceatannol treatment of human platelets completely inhibited platelet adhesion to immobilized fibrinogen. The discrepancy in extent of integrin dysfunction between murine and human platelet models may be due to lack of specificity of piceatannol, because this compound inhibited the activity of Src and FAK as well as Syk and also reduced tyrosine phosphorylation of multiple platelet proteins. These results provide genetic evidence that Syk plays a role in alphaIIbbeta3 signaling in platelets and pharmacological evidence that, although piceatannol also inhibits alphaIIbbeta3 signaling, it does so by inhibtion of multiple protein tyrosine kinases.

Animals↗
PubMed1999

The IGF-I amino-terminal tripeptide glycine-proline-glutamate (GPE) is neuroprotective to striatum in the quinolinic acid lesion animal model of Huntington's disease.

Huntington's disease is an incurable genetic neurological disorder characterized by the relatively selective degeneration of the striatum. Lesioning of the striatum in rodents using the excitatory amino acid agonist, quinolinic acid (QA), effectively mimics the human neuropathology seen in Huntington's disease. Using this animal model of Huntington's disease, we investigated the ability of the insulin-like growth factor-I (IGF-I) amino-terminal tripeptide glycine-proline-glutamate (GPE) to protect striatal neurons from degeneration. Adult rats received a single unilateral intrastriatal injection of QA (100 nmol) and then daily injection of either vehicle or GPE (0.3 microgram/microliter/day) into the striatum for 7 days. QA at this dose resulted in a partial lesioning of the striatum after 7 days to approximately 50% of cells of unlesioned levels in vehicle-treated animals. The major striatal neuronal phenotype, GABAergic projection neurons, were identified by immunocytochemical labeling of either glutamate decarboxylase 67 (GAD(67)) or the calcium binding protein calbindin in alternate sections. Treatment with GPE for 7 days reversed the loss in projection neurons when assessed by counts of calbindin-stained cells; however, these rescued cells did not regain immunologically detectable levels of GAD(67). GPE also significantly reversed the phenotypic degeneration of cholinergic interneurons identified by immunolabeling for choline acetyltransferase (ChAT) and NADPH diaphorase interneurons identified histochemically. GPE treatment failed to rescue the calcium binding protein interneuron populations of parvalbumin and calretinin neurons. These findings reveal that exogenous administration of GPE selectively prevents excitotoxin induced phenotypic degeneration of striatal projection neurons and cholinergic and NADPH diaphorase interneurons in an animal model of Huntington's disease.

Animals↗
PubMed1999

Activity and injury-dependent expression of inducible transcription factors, growth factors and apoptosis-related genes within the central nervous system.

This review primarily discusses work that has been performed in our laboratories and that of our direct collaborators and therefore does not represent an exhaustive review of the current literature. Our aim is to further discuss the role that gene expression plays in neuronal plasticity and pathology. In the first part of this review we examine activity-dependent changes in the expression of inducible transcription factors (ITFs) and neurotrophins with long-term potentiation (LTP) and kindling. This work has identified particular ITFs (Krox-20 and Krox-24) and neurotrophin systems (particularly the brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase-B, Trk-B system) that may be involved in stabilizing long-lasting LTP (i.e. LTP3). We also show that changes in the expression of other ITFs (Fos, Jun-D and Krox-20) and the BDNF/trkB neurotrophin system may play a central role in the development of hippocampal kindling, an animal model of human temporal lobe epilepsy. In the next part of this review we examine changes in gene expression after neuronal injuries (ischemia, prolonged seizure activity and focal brain injury) and after nerve transection (axotomy). We identify apoptosis-related genes (p53, c-Jun, Bax) whose delayed expression selectively increases in degenerating neurons, further suggesting that some forms of neuronal death may involve apoptosis. Moreover, since overexpression of the tumour-suppressor gene p53 induces apoptosis in a wide variety of dividing cell types we speculate that it may perform the same function in post-mitotic neurons following brain injuries. Additionally, we show that neuronal injury is associated with rapid, transient, activity-dependent expression of neurotrophins (BDNF and activinA) in neurons, contrasting with a delayed and more persistent injury-induced expression of certain growth factors (IGF-1 and TGFbeta) in glia. In this section we also describe results linking ITFs and neurotrophic factor expression. Firstly, we show that while BDNF and trkB are induced as immediate-early genes following injury, the injury-induced expression of activinA and trkC may be regulated by ITFs. We also discuss whether loss of retrograde transport of neurotrophic factors such as nerve growth factor following nerve transection triggers the selective and prolonged expression of c-Jun in axotomized neurons and whether c-Jun is responsible for regeneration or degeneration of these axotomized neurons. In the last section we further examine the role that gene expression may play in memory formation, epileptogenesis and neuronal degeneration, lastly speculating whether the expression of various growth factors after brain injury represents an endogenous neuroprotective response of the brain to injury. Here we discuss our results which show that pharmacological enhancement of this response with exogenous application of IGF-1 or TGF-beta reduces neuronal loss after brain injury.

Animals↗
PubMed1999

Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington's disease.

Huntington disease is characterized by the selective loss of striatal neurons, particularly of medium-sized spiny glutamate decarboxylase67 staining/GABAergic projection neurons which co-contain the calcium binding protein calbindin. Lesioning of the adult rat striatum by intrastriatal injection of the N-methyl-D-aspartate receptor agonist quinolinic acid (100 nmol) results in a pattern of striatal neuropathology seven days later that resembles that seen in the Huntington brain. Using this animal model of human Huntington's disease we investigated the effect of daily intrastriatal infusion of the nerve cell survival molecule ActivinA (single bolus dose of 0.73 microg daily for seven days) on the quinolinic acid-induced degeneration of various striatal neuronal phenotypes. By seven days, unilateral intrastriatal infusion of quinolinic acid produced a partial but significant loss (P < 0.01) in the number of striatal neurons immunoreactive for glutamate decarboxylase (to 51.0+/-5.8% of unlesioned levels), calbindin (to 58.7+/-5.1%), choline acetyltransferase (to 68.6+/-6.1%), NADPH-diaphorase (to 47.4+/-5.4%), parvalbumin (to 58.8+/-4.1%) and calretinin (to 60.6+/-8.6%) in adult rats that were administered intrastriatal phosphate-buffered saline for seven days following quinolinic acid. In contrast, in rats that received intrastriatal recombinant human ActivinA once daily for seven days following quinolinic acid, phenotypic degeneration was significantly attenuated in several populations of striatal neurons. Treatment with ActivinA had the most potent protective effect on the striatal cholinergic interneuron population almost completely preventing the lesion induced decline in choline acetyltransferase expression (to 95.1+/-5.8% of unlesioned levels, P < 0.01). ActivinA also conferred a significant protective effect on parvalbumin (to 87.5+/-7.7%, P < 0.01) and NADPH-diaphorase (to 77.5+/-7.5%, P < 0.01) interneuron populations but failed to prevent the phenotypic degeneration of calretinin neurons (to 56.6+/-5.5%). Glutamate decarboxylase67 and calbindin-staining nerve cells represent largely overlapping populations and both identify striatal GABAergic projection neurons. We found that ActivinA significantly attenuated the loss in the numbers of neurons staining for calbindin (to 79.7+/-6.6%, P < 0.05) but not glutamate decarboxylase67 (to 61.1+/-5.9%) at seven days following quinolinic acid lesioning. Taken together these results suggest that exogenous administration of ActivinA can rescue both striatal interneurons (labelled with choline acetyltransferase, parvalbumin, NADPH-diaphorase) and striatal projection neurons (labelled by calbindin) from excitotoxic lesioning with quinolinic acid. Longer-term studies will be required to determine whether these surviving calbindin-expressing projection neurons recover their ability to express the glutamate decarboxylase67/GABAergic phenotype. These results therefore suggest that treatment with ActivinA may help to prevent the degeneration of vulnerable striatal neuronal populations in Huntington's disease.

Activins↗
PubMed1999

The small GTP-binding protein R-Ras can influence integrin activation by antagonizing a Ras/Raf-initiated integrin suppression pathway.

The rapid modulation of ligand-binding affinity ("activation") is a central property of the integrin family of cell adhesion receptors. The small GTP-binding protein Ras and its downstream effector kinase Raf-1 suppress integrin activation. In this study we explored the relationship between Ras and the closely related small GTP-binding protein R-Ras in modulating the integrin affinity state. We found that R-Ras does not seem to be a direct activator of integrins in Chinese hamster ovary cells. However, we observed that GTP-bound R-Ras strongly antagonizes the Ras/Raf-initiated integrin suppression pathway. Furthermore, this reversal of the Ras/Raf suppressor pathway does not seem to be via a competition between Ras and R-Ras for common downstream effectors or via an inhibition of Ras/Raf-induced MAP kinase activation. Thus, R-Ras and Ras may act in concert to regulate integrin affinity via the activation of distinct downstream effectors.

Animals↗
PubMed1998

The death effector domain of PEA-15 is involved in its regulation of integrin activation.

Increased integrin ligand binding affinity (activation) is triggered by intracellular signaling events. A Ras-initiated mitogen-activated protein kinase pathway suppresses integrin activation in fibroblasts. We used expression cloning to isolate cDNAs that prevent Ras suppression of integrin activation. Here, we report that PEA-15, a small death effector domain (DED)-containing protein, blocks Ras suppression. PEA-15 does not block the capacity of Ras to activate the ERK mitogen-activated protein kinase pathway. Instead, it inhibits suppression via a pathway blocked by a dominant-negative form of the distinct small GTPase, R-Ras. Heretofore, all known DEDs functioned in the regulation of apoptosis. In contrast, the DED of PEA-15 is essential for its capacity to reverse suppression of integrin activation. Thus, certain DED-containing proteins can regulate integrin activation as opposed to apoptotic protease cascades.

Amino Acid Sequence↗
PubMed1998

3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration.

3-Nitropropionic acid (3-NP) is a mitochondrial toxin which interferes with ATP synthesis. Accidental ingestion of 3-NP by humans as well as other mammals results in neuronal degeneration within the basal ganglia and movement dysfunction characterized by dystonia, chorea, and hypokinesia. The selective degeneration of structures of the basal ganglia occurs despite the non-selective impairment of energy metabolism throughout the brain and body. These effects of 3-NP are shared with the genetic disorder Huntington's disease (HD), which is characterized by progressive neurodegeneration of the basal ganglia and choreic motor dysfunction. These similarities have prompted further investigation of 3-NP as an animal model of HD. Metabolic compromise with 3-NP causes neurodegeneration that involves three interacting processes: energy impairment, excitotoxicity, and oxidative stress. This triplet of cooperative pathways of neurodegeneration helps to explain 3-NP's regional selectivity of neurotoxicity to the basal ganglia. This mini-review will focus on the actions of 3-NP and the related compound, malonic acid (MA), in the central nervous system, with an emphasis on the more current findings regarding their mechanisms of action.

Animals↗
PubMed1998

The effects of post-weaning progestagen treatment (Regumate) of early-weaned primiparous sows on subsequent reproductive performance.

This study investigated the effects of feeding the orally active progestagen, altrenogest (Regumate) post-weaning on the subsequent reproductive performance of early weaned sows. Ninety (90) Large White/Landrace first parity sows were randomly assigned to three treatments. Treatment 1 (EW) and treatment 3 (CW) sows were weaned on day 12 and day 24 post-partum, respectively while treatment 2 sows (EW-R) were weaned on day 12 post-partum and received an individual daily dose of 20 mg of Regumate on days 13 to 24 post-partum inclusive. Each sow was mated naturally at least twice at the first post-weaning or post-treatment oestrus and slaughtered on days 25-28 of pregnancy to determine the number of corpora lutea and embryos. Regumate-to-oestrus and weaning-to-oestrus intervals were similar for EW-R and CW sows (6.2 vs. 5.6 days). However, both intervals were significantly shorter (P < 0.01) than the weaning-to-oestrus interval of EW sows (7.3 days). An excellent synchronization of oestrus was achieved with Regumate treatment with 97% of treated sows in oestrus within 7 days of Regumate withdrawal compared with 64% for EW sows (P < 0.01) and 87% for CW sows (P > 0.05). Treatment with Regumate resulted in a significant increase in ovulation rate (16.9 vs. 15.4 and 14.9 for treatments EW-R, EW and CW, respectively; P < 0.05) and a non-significant increase in early embryonic survival (77% vs. 68% vs. 68% for treatments EW-R, EW and CW, respectively; P > 0.05). These results indicate that Regumate feeding is a potential management tool to alleviate the diminished reproductive performance associated with early weaning regimes since it leads to successful control of oestrus, higher ovulation and embryo survival rates and thus a greater potential litter size.

Animals↗
PubMed1998

The effect of repeated boar exposure on cortisol secretion and reproduction in gilts.

It has been proposed that short-term activation of the hypothalamo-pituitary adrenal axis, with a consequent increase in the secretion of cortisol, amy disrupt the endocrine events prior to ovulation and thereby impair reproduction in females. We investigated this concept in gilts in which oestrus was detected by introduction to boars, where intense physical contact is possible, or by applying pressure to the back of gilts (back-pressure test) during fence-line exposure to boars, where intense physical contact is prohibited. We expected that there would be a greater release of cortisol and that reproduction would be inhibited in gilts introduced to boars compared to gilts in which the back-pressure test was used. As expected, introduction of gilts to boars resulted in a significant transient increase in plasma concentrations of cortisol while there was no significant effect of using the back-pressure test on plasma cortisol. Nevertheless, introduction of gilts to boars did not impair reproduction and there was no effect of method of detecting oestrus on duration of oestrus, sexual receptivity, fertility or fecundity. The length of the oestrous cycle was decreased and ovulation rate increased in gilts that were introduced to boars compared to gilts that underwent the back-pressure test, indicating that introduction of gilts to boars may have stimulated these aspects of reproduction. These stimulatory effects may have been due to an increased exposure of gilts to sexual behaviour and stimuli from boars when introduced to boars and/or to stimulatory effects of the hypothalamo-pituitary adrenal axis on some aspects of reproduction.

Adrenal Glands↗
PubMed1998

Metabolic compromise with systemic 3-nitropropionic acid produces striatal apoptosis in Sprague-Dawley rats but not in BALB/c ByJ mice.

Metabolic compromise with systemic 3-nitropropionic acid (3-NP) results in the degeneration of striatal cells, mimicking the pathology of Huntington's disease (HD). Here we show that 10-week- and 8-month-old BALB/c ByJ mice show an unexpected striatal resilience to single and multiple systemic injections of 3-NP, while Sprague-Dawley rats are vulnerable, albeit in a variable manner. Identification of lesions was made by staining of DNA fragmentation with terminal deoxytransferase-mediated dUTP-biotin nick-end labeling (TUNEL) and hematoxylin/eosin, 1-10 days after injection. Quantitative imaging of histochemistry for succinate dehydrogenase (SDH) activity, the target of 3-NP inhibition, revealed that vulnerable rats reached maximal inhibition in brain at 1 day after 3-NP, whereas mice and resilient rats took 7 days to reach maximal inhibition. All groups of animals reached similar maximal decreases in SDH activity in striatum and cortex. Remarkably, only the fast decline in SDH activity seen in vulnerable rats was associated with TUNEL labeling. In addition, vulnerable rats developed a region within striatum where SDH activity was fully depleted and a similarly depleted region in CA1 hippocampus. While mice did not develop this region in striatum, some developed one in CA1. These regions of SDH depletion in both structures were associated with widespread TUNEL staining, with maximal labeling at 3 days after 3-NP. The existence of an animal strain resilient to 3-NP suggests that there are mediating factors involved in the preferential vulnerability of striatum to metabolic lesioning. The identification of these factors could provide strategies for therapeutic intervention in HD.

Aging↗